Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Basal cell carcinoma of the vulva: treatment with Mohs micrographic surgery.

Vulval basal cell carcinomas (BCCs) are rare, representing < 5% of vulval malignancies and 1% of all BCCs. They often present with nonspecific symptoms and features that lead to large, poorly circumscribed and late-presenting lesions. Current and conventional treatments used to treat vulval BCC include cryotherapy, imiquimod and excision. However, recurrence rates as high as 20% have been reported with these treatments. Furthermore, there are no current clinical guidelines for their management. We present the first reported series of patients with vulval BCC treated with Mohs micrographic surgery (MMS). We report seven cases of vulval BCC treated with MMS at a tertiary referral centre over 3 years. Follow-up was performed at 3 months and up to 3 years. Our series demonstrates that there were no postoperative complications, functional sequelae or recurrences up to the 3-year follow-up. We therefore recommend that MMS should be considered in the management of vulval BCCs.

Diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis is diagnosed based on the 2010 Rheumatoid Arthritis Classification Criteria whereby rheumatoid factor and anti-citrullinated protein antibody are the serological markers included in these criteria. Anti-RA33 antibody has the potential to provide additional diagnostic value in rheumatoid arthritis. The aim of this study is to determine the diagnostic performance of anti-RA33 antibody as a serological marker for rheumatoid arthritis. MATERIAL AND METHODS: Thirtyfour patients with rheumatoid arthritis and 34 non-rheumatoid arthritis individuals were included in this cross-sectional study. Anti-RA33 antibody and rheumatoid factor were performed on all samples. RESULTS: The sensitivity, specificity, positive and negative predictive value for anti-RA33 antibody and rheumatoid factor were 41.1%, 97.1%, 93.3%, 62.3% and 64.7%, 79.4%, 75.9%, 69.2% respectively. The overall sensitivity and specificity if either anti-RA33 antibody or rheumatoid factor are positive were 79.4% and 76.47% respectively. CONCLUSION: Anti-RA33 antibody showed good specificity and positive predictive value and could be considered as a potential serological marker for rheumatoid arthritis diagnosis.

Emergence of Multidrug- and Pandrug- Resistant Pseudomonas aeruginosa from Five Hospitals in Qatar.

BACKGROUND: A global rise in multidrug-resistant (MDR) nosocomial infections has led to a significant increase in morbidity and mortality. MDR Gram-negative bacteria (GNB) are recognised for rapidly developing drug resistance. Despite Pseudomonas aeruginosa being the second most common GNB isolated from healthcare associated infections, the magnitude of MDR P. aeruginosa (MDR-PA) has not been evaluated in Qatar. AIM: To assess the prevalence and antimicrobial susceptibility patterns of MDR-PA from 5 major hospitals in Qatar. METHODS: A total of 2533 P. aeruginosa clinical isolates were collected over a one-year period. MDR-PA was defined as resistance to at least one agent of ≥ 3 antibiotic classes. Clinical and demographic data were collected prospectively. FINDINGS: The overall prevalence of MDR-PA isolates was 8.1% (205/2533); the majority of isolates were from patients exposed to antibiotics during 90 days prior to isolation (85.4 %, 177/205), and the infections were mainly hospital-acquired (95.1%, 195/205) with only 4.9% from the community. The majority of MDR-PA isolates were resistant to cefepime (96.6%, 198/205), ciprofloxacin, piperacillin/tazobactam (91%, 186/205), and meropenem (90%, 184/205). Patient comorbidities with MDR-PA were diabetes mellitus (47.3%, n=97), malignancy (17.1%, n=35), end-stage renal disease (13.7%, n=28) and heart failure (10.7%, n=22). CONCLUSION: There was a significant prevalence of MDR-PA in Qatar, primarily from healthcare facilities and associated with prior antibiotic treatment. There was an alarming level of antimicrobial resistance to carbapenems. Our results are part of a national surveillance of MDR to establish effective containment plans.

Hepatitis B seroepidemiology and booster vaccination in pre-clinical medical students in a Malaysian university.

INTRODUCTION: Infant hepatitis B vaccination was introduced into the Expanded Programme on Immunisation (EPI) in Malaysia in 1989. This study aimed to investigate seroprevalence of hepatitis B among UKM pre-clinical medical students, born between 1991 and 1995, and had their infant vaccination more than 20 years ago. MATERIALS AND METHODS: A prospective, cross-sectional study involving 352 students, comprising 109 (31.0%) males and 243 (69.0%) females. Blood specimens were tested for anti-HBs, where levels of ≥10 mIU/mL was considered reactive and protective. Students with non-reactive levels were given a 20 µg HBV vaccine booster. Anti-HBs levels were tested six weeks after the first booster dose. Those with anti-HBs <10 mIU/mL were then given another two booster doses, at least one month apart. Anti-HBs levels were tested six weeks after the third dose. RESULTS: Ninety-seven students (27.6%) had anti-HBs ranging from 10 to >1000 mIU/mL while 255 (72.4%) had anti-HBs <10 mIU/mL. After one booster dose, 208 (59.1%) mounted anti-HBs ≥10 mIU/mL. Among the remaining 47 (13.3%), all except two students (0.6%) responded following completion of three vaccination doses. They were negative for HBsAg and anti-HBcore antibody, thus regarded as non-responders. CONCLUSIONS: Anti-HBs levels waned after 20 years post-vaccination, where more than 70% were within non-reactive levels. For healthcare workers, a booster dose followed by documenting anti-HBs levels of ≥10 mIU/mL may be recommended, to guide the management of post-exposure prophylaxis. Pre-booster anti-HBs testing may not be indicated. Serological surveillance is important in long-term assessment of HBV vaccination programs. No HBV carrier was detected.

Intrafamilial phenotypic heterogeneity of epidermolytic ichthyosis associated with a new missense mutation in keratin 10.

Mutations in the keratin 10 gene (KRT10) have been shown to underlie several forms of epidermolytic ichthyosis (EI), including generalized, annular and naevoid variants. We investigated an autosomal dominant pedigree with ichthyosis in which there was intrafamilial clinical heterogeneity, with the affected individual family members presenting with features of either erythrokeratoderma progressiva, annular EI, localized or superficial EI, or more generalized EI. Sanger sequencing identified a new heterozygous missense mutation (c.457C>A; p.Leu153Met) in KRT10 in all affected individuals. No additional mutations were identified in the genes for keratin 1 (KRT1) keratin 2 (KRT2), connexin 31 (GJB3) or connexin 30.3 (GJB4) that might account for the clinical heterogeneity seen in this family. Our findings illustrate the intrafamilial variability in phenotype and diverse clinical presentations that can occur in EI resulting from a single mutation in KRT10.

Genotypic diversity of Pseudomonas aeruginosa in cystic fibrosis siblings in Qatar using AFLP fingerprinting.

Pseudomonas aeruginosa is one of the primary pathogens in patients with cystic fibrosis (CF) and a major cause of morbidity and mortality. Reports of the spread of epidemic or transmissible strains of P. aeruginosa within and across CF centers raised the possibility of clonal spread among siblings with CF. This work reports the genotypic relatedness of P. aeruginosa in CF patients with the CFTR I1234V mutation, and to determine whether the genotypes are identical among CF siblings and among different families with the same CFTR mutation. Sixty-six P. aeruginosa isolates were obtained from sputa/deep-pharyngeal swabs from 27 CF patients belonging to 17 families. Genotypic relatedness was assessed using amplified fragment-length polymorphism (AFLP) fingerprinting. Twenty-three distinct genotypes of P. aeruginosa were identified. Eleven families each had one distinct genotype. In the other 6 families more than one genotype was observed; 3 families each showed two genotypes, 2 families each had three genotypes and 1 family had four genotypes of P. aeruginosa. In several cases, siblings with CF from the same family harbored the same strain of P. aeruginosa, which were different from the genotypes in other families. On the other hand, there was an overlap in P. aeruginosa between closely related families. Some patients show persistent colonization with the same genotype of P. aeruginosa over the longitudinal period. The presence of the same genotypes in siblings of the same family and closely related families suggests cross-transmission of P. aeruginosa or acquisition from common environmental exposure.

A comparative evaluation of dengue diagnostic tests based on single-acute serum samples for laboratory confirmation of acute dengue.

A prospective study was carried out to evaluate the sensitivity of dengue NS1 antigen-capture ELISA in comparison with dengue virus isolation, conventional RT-PCR and real-time RT-PCR for laboratory confirmation of acute dengue based on single-acute serum samples. Four primary healthcare centres were involved to recruit patients with clinical diagnosis of dengue illness. Patient's demographic, epidemiological and clinical information were collected on a standardized data entry form and 5 ml of venous blood was collected upon consent. In the laboratory, six types of laboratory tests were performed on each of the collected acute serum sample. Of the 558 acute serum samples collected from 558 patients with clinical diagnosis of dengue from mid-August 2006 to March 2009, 174 serum samples were tested positive by the dengue NS1 antigen-capture ELISA, 77 by virus isolation, 92 by RT-PCR and 112 by real-time RT-PCR. A total of 190 serum samples were tested positive by either one or a combination of the four methods whereas, only 59 serum samples were tested positive by all four methods. Thus, based on single-acute serum samples, 190 of the 558 patients (34.1%) were laboratory-confirmed acute dengue. The overall test sensitivity was 91.6%, 40.5%, 48.4% and 58.9% for dengue NS1 antigen-capture ELISA, virus isolation, conventional RT-PCR and real-time RT-PCR respectively. Statistically, dengue NS1 antigen-capture ELISA was the most sensitive and virus isolation was the least sensitive test for the laboratory confirmation of acute dengue based on single-acute serum specimens. Real-time RT-PCR was significantly more sensitive than the conventional RT-PCR.

Calcific panniculitis in adult-onset dermatomyositis.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with characteristic cutaneous features. Panniculitis is a rarely reported clinical finding in this condition. This report describes two cases of adult-onset DM complicated by severe calcific panniculitis. In both cases, the associated pain and loss of function seemed to be best managed on combination anti-malarial therapy with mepacrine and hydroxychloroquine.

Faecal elastase-1 concentration in cystic fibrosis patients with CFTR I1234V mutation.

AIM: To assess the exocrine pancreatic function among cystic fibrosis patients with cystic fibrosis trans-membrane conductance regulator (CFTR) I1234V mutation. METHODS: Cross-sectional study of 40 cystic fibrosis patients with homozygous CFTR I1234V mutation belonging to a large Arab kindred family and 25 healthy subjects as a control group over a period of 12 mo. Assessment of their exocrine pancreatic function was performed by measuring faecal elastase-1 (FE1) concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in CF patients compared to healthy subjects. The results were compared with those obtained from a second laboratory using another commercial ELISA (ScheBo; Biotech, Germany) that uses two monoclonal antibodies against different specific epitopes of human pancreatic elastase. RESULTS: All CF patients with CFTR I1234V mutation had normal levels of faecal elastase 1. No significant difference was found between the two methods for the CF groups or between the CF patients with and without pancreatic enzyme replacement. CONCLUSION: Cystic fibrosis with homozygous CFTR I1234V mutation is associated with pancreatic sufficiency. Assessment of exocrine function using polyclonal antibodies does not significantly differ from that using two monoclonal antibodies against different specific epitopes of human pancreatic elastase.

A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar.

AIM: To describe the clinical spectrum of anomalies of a new type of Ehlers-Danlos syndrome in 32 patients from a large inter-related extended family in Qatar. METHODS: Among the 32 patients (from 22 families), there were 6 affected pairs of siblings and 2 families with 3 affected siblings. The male to female ratio was 2:1, ages ranging from birth to 18 y (mean 7.4 y). RESULTS: Anomalies included a variable degree of skin hyperextensibility, hypermobility of small and large joints, and tortuous systemic arteries. Peculiar facial features included epicanthic folds, flat saggy cheeks, elongated faces and micrognathia. The combination of an elongated aortic arch and tortuous brachiocephalic arteries was seen in 30 patients (93.8%), aneurysm of the ascending aorta in 3 patients (9.4%), bifid pulmonary artery in 27 patients (84.4%) and multiple severe peripheral stenosis of the right and/or left pulmonary artery in 7 patients (21.9%). A prominent aortic knuckle was observed on the chest roentgenograms of 30 patients (93.8%); inguinal hernia in 11 patients (34%), diaphragmatic hernia and/or hiatus hernia in 7 patients (21.9%); and laryngo-tracheomalacia in 2 patients (6.3%). Generalized muscle hypotonia was found in 15 neonates (46.9%). Parental consanguinity involved in all the patients was traced to a common ancestor from a large Bedouin tribe in Qatar. These patients are at risk for potentially catastrophic arterial rupture. Linkage to the major loci involved in Ehlers-Danlos syndrome and other connective tissue disorders, such as Cutis Laxa, Familial Aneurysm, and Osteogenesis imperfecta, was excluded by using specific DNA markers, confirming the uniqueness of this disorder. CONCLUSION: The study describes a large cohort of patients from the same closely related family, sharing peculiar dysmorphisim and consistent radiological and echocardiographic features different from known types of Ehlers-Danlos syndrome. As known loci involved in Ehlers-Danlos syndrome and other connective tissue disorders were excluded by specific DNA markers, this appears to be a new type of Ehlers-Danlos syndrome or even a new syndrome.

Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar with cystic fibrosis mutation (I1234V).

Twenty-nine subjects (17 families) with cystic fibrosis belonging to the same Bedouin tribe were screened for cystic fibrosis transmembrane regulator gene mutations (CFTR). Homozygous I1234V mutation in exon 19 was identified in all families with a relatively high rate of consanguinity (96.6 per cent). The homozygous I1234V mutation tended to present with a variable degree of pulmonary disease, pancreatic insufficiency and electrolyte imbalance. Homozygous I1234V was found to be a common mutation in the studied Bedouin tribe in Qatar.

National study on the prevalence of iodine deficiency disorders among schoolchildren 8-12 years of age in Bahrain.

A cross-sectional survey of primary-school children in Bahrain was conducted to estimate the prevalence of goitre and iodine deficiency according to age, sex and area of residence. During January-May 1999, 1600 children were randomly chosen from all government schools. Children were examined for goitre and of those, 50% were randomly selected for urinary iodine level assessment. Only 26 children (1.7%) had goitre. Although median urinary iodine was above 100 microg/L, 121 of 749 children (16.2%) had low urinary iodine levels. Although iodine deficiency does not pose a significant public health problem in Bahrain, education about the nutritional value of iodized salts in the prevention of this disorder could increase public awareness.

Cystic fibrosis in a large kindred family in Qatar.

We describe 45 patients with cystic fibrosis (CF), diagnosed between June 1987 and May 1999, seen at the Hamad Medical Corporation, Qatar in the Arabian Gulf. Twenty-six of 32 families in the study were related and belonged to the same Bedouin tribe. The parents of 98% of these cases were consanguineous. Metabolic alkalosis and/or hypo-electrolytaemia were found in a large proportion of infants with CF. Cystic fibrosis in Qatari children is phenotypically variable with mild to moderate respiratory symptoms, and none of them died during this study. Among the non-Arabic-Asian patients, pulmonary symptoms were more severe, Pseudomonas colonization was earlier, pancreatic insufficiency occurred in infancy and four died in early life.